Tumor Specific Plasma DNA

NCT01617915 | Completed DMC

• 1 other identifier: D12127
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

In 2011, there was an estimated 233,000 cases of invasive breast cancer, and 39,970 deaths from breast cancer in the United States. The vast majority of patients are diagnosed with Stage I-III resectable and potentially curable disease, and for these patients, the most pressing questions are whether adjuvant endocrine or chemotherapy are indicated, and if so, how to determine whether these treatments are working. Adjuvant systemic therapy reduces relative recurrence rates by 30-50%, depending on the age of the patient and tumor characteristics. However, patients with early stage disease often do not bear measurable markers of disease such as an elevated cancer antigen 27-29 (CA27.29) or circulating tumor cells. Patients with early stage breast cancer are typically treated with adjuvant therapy based on historical evidence showing that such therapy prolongs survival in this population. Lung cancer is the most common malignancy and the leading cause of cancer-related death in the U.S. Approximately 220,000 new cases of lung cancer are diagnosed in the U.S. every year. Unfortunately, lung cancers are often diagnosed at later stages than breast cancer, due in part to little/no effective screening for lung cancer. As with breast cancer, patients are commonly treated with chemotherapeutic agents, but treatment regimens can take several weeks to months to elicit clinically detectable anti-tumor effects. A biomarker to assess early tumor response to therapy would benefit this patient population. The contents of dying tumor cells can be detected in the bloodstream, and this may be enhanced by the leaky vasculature of solid tumors. Protein biomarkers of tumor cell death are difficult to detect due to the complex nature of plasma and the lack of technical sensitivity. In contrast, DNA is easier to detect through polymerase chain reaction (PCR) amplification. Indeed, circulating tumor DNA has been detected in plasma from patients with osteosarcoma, breast cancer, and colorectal cancer. Until recently, it was impractical to develop an assay to routinely quantify circulating tumor DNA due to heterogeneity between patients and tumors. Advances in genomic technology now permit sequencing a tumor genome to identify patient-specific genomic aberrations. Major genomic alterations (i.e., insertions, amplifications, deletions, inversions, translocations) can be readily detected using PCR primers which will recognize tumor DNA but not normal DNA. While this strategy may be generally applicable to diverse types of solid tumors, two issues are apparent in breast cancer. Firstly, the incidence of chromosomal rearrangements varies widely. Whole-genome sequencing of 15 breast tumors revealed a range of 1-231 major genomic alterations (mean= 68), where 2 tumors had 1 alteration, and 9 tumors had \> 20 alterations. Single-base point mutations are more common but difficult to reliably detect using PCR. Therefore, the investigators must consider that a small subset of patients may have a limited number of genomic alterations available for this assay. Secondly, intratumoral heterogeneity may mean that some genomic alterations are not present in every tumor cell. Such heterogeneity has been inferred from FISH and immunohistochemistry (IHC) studies for many years, and is now being verified at the genomic level. The investigators must consider that only a subpopulation of tumor cells may be sensitive to cytotoxic therapy, so changes in the levels of circulating tumor DNA may only be reflected with analysis of genomic alterations specific to the sensitive cells.

Conditions

Breast Cancer; Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Circulating tumor levels correlation to response

  To determine whether acute increases in the levels of circulating tumor DNA correlate with response to chemotherapy in patients with breast cancer.

  6 months

Secondary Outcomes (5)

• Circulating tumor DNA following surgery

  6 months

• To determine optimal timing for detection of circulating tumor DNA

  6 months

• Circulating tumor DNA detection following surgery

  6 months

• Circulating tumor DNA correlation with pathologic complete response

  6 months

• Circulating tumor DNA correlation with clinical evidence of disease recurrence or progression

  6 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Breast and Lung cancer patients

You may qualify if:

• Women or men \> age 18.
• Ability to give informed consent
• Archived tumor tissue must be available for genetic analysis.
• Patients with early-stage breast cancer
• Histologic documentation of invasive breast cancer by core needle or incisional biopsy.
• The invasive cancer must be either:
• triple-negative with both estrogen and progesterone receptor staining present in fewer than 10% of invasive cancer cells by IHC, and HER2-negative defined as IHC 0-1+, or with a FISH ratio of \<1.8 if IHC is 2+ or if IHC has not been done.
• \*HER2-positive with IHC 3+ or a FISH ratio of \>2.2.
• Clinical Stage II-III invasive breast cancer with the intent to treat with:
• pretreatment mammography, ultrasound, and breast MRI for staging
• pretreatment axillary staging
• neoadjuvant treatment with DNA-damaging chemotherapy (with or without HER2- directed therapy)
• post-chemotherapy breast MRI
• surgical resection of the primary tumor with an axillary dissection for one or more positive nodes after neoadjuvant chemotherapy
• Patients with multicentric or bilateral disease are eligible if the target lesion(s) meet the other eligibility criteria.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gary N Schwartz, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 10, 2012
• First Posted: June 13, 2012
• Study Start: October 1, 2012
• Primary Completion: May 7, 2021
• Study Completion: May 7, 2021
• Last Updated: August 17, 2021

Record last verified: 2021-08

Locations

US (1)